Systemic Light-Chain Amyloidosis: Evolving Diagnostic Paradigms and Emerging Therapeutic Strategies Beyond ANDROMEDA

Background: Systemic light-chain (AL) amyloidosis is a clonal plasma-cell disorder whose prognosis hinges on early diagnosis and rapid deepening of haematologic response. The ANDROMEDA trial established daratumumab plus bortezomib, cyclophosphamide, and dexamethasone (CyBorD) as a new standard of first-line care, yet diagnostic delays persist and relapsed/refractory disease remains therapeutically challenging. This systematic review and meta-analysis synthesizes evolving diagnostic paradigms and evaluates emerging therapeutic strategies beyond ANDROMEDA. Methods: This review was conducted per PRISMA 2020. Randomized trials, cohort studies, and case series (n ≥ 10) reporting on diagnostic modalities or therapies for AL amyloidosis in adults were eligible. Two independent reviewers performed screening, data extraction, and risk-of-bias assessment (RoB 2, ROBINS-I). Random-effects meta-analysis pooled [complete haematologic response (CHR), organ response, overall survival (OS), and grade ≥ 3 adverse events]; heterogeneity was evaluated with I², and certainty appraised with GRADE. Result and Conclusions: Diagnostic innovation is central to improving outcomes in AL amyloidosis, and post-ANDROMEDA strategies show promising efficacy and acceptable safety. Standardization of response criteria and prospective comparative data are needed. These findings support a biomarker-guided, risk-adapted therapeutic framework.